Under conditions of caloric stress such as seen in diabetes mellitus or during any disease or healing proess, the large mass of muscle tissue appears to play an important role in the substrate balance of the whole organism by appropriate changes in the substrates which it consumes. The cause of these changes have been credited to changed substrate delivery or changed endocrine milieu. Very probably both factors play a role, with the simple substrate change predominating in the short term and the endocrine changes being more important to the long term adaptive responses. The goal of the work proposed here is to develop a method for quantitating the simultaneous contributions of carbohydrate, lipid and amino acids to oxidative metabolism in the slow oxidative fibers of rat soleus muscle, and then to systematically evaluate the effects of changing substrate levels and finally the interaction of insulin with the direct substrate effects. The analysis will be based on a steady state model of labelled substrate use which is most sensitive to metabolic branch points. Therefore both endogenous and exogenous substrate turnover can be quantitated.